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PDBsum entry 2nw7

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
2nw7
Jmol
Contents
Protein chains
259 a.a. *
Ligands
HEM ×4
Waters ×142
* Residue conservation analysis
PDB id:
2nw7
Name: Oxidoreductase
Title: Crystal structure of tryptophan 2,3-dioxygenase (tdo) from xanthomonas campestris in complex with ferric heme. Northeast structural genomics target xcr13
Structure: Tryptophan 2,3-dioxygenase. Chain: a, b, c, d. Engineered: yes
Source: Xanthomonas campestris pv. Campestris. Organism_taxid: 340. Strain: pv. Campestris. Atcc: 33913. Gene: xcc0432. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.70Å     R-factor:   0.257     R-free:   0.263
Authors: F.Forouhar,J.L.R.Anderson,C.G.Mowat,A.Hussain,C.Bruckmann, S.J.Thackray,J.Seetharaman,T.Tucker,C.K.Ho,L.C.Ma, K.Cunningham,H.Janjua,L.Zhao,R.Xiao,J.Liu,M.C.Baran, T.B.Acton,B.Rost,G.T.Montelione,S.K.Chapman,L.Tong, Northeast Structural Genomics Consortium (Nesg)
Key ref:
F.Forouhar et al. (2007). Molecular insights into substrate recognition and catalysis by tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A, 104, 473-478. PubMed id: 17197414 DOI: 10.1073/pnas.0610007104
Date:
14-Nov-06     Release date:   19-Dec-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8PDA8  (T23O_XANCP) -  Tryptophan 2,3-dioxygenase
Seq:
Struc:
298 a.a.
259 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.13.11.11  - Tryptophan 2,3-dioxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Tryptophan Catabolism
      Reaction: L-tryptophan + O2 = N-formyl-L-kynurenine
L-tryptophan
+ O(2)
= N-formyl-L-kynurenine
      Cofactor: Heme
Heme
Bound ligand (Het Group name = HEM) matches with 95.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   4 terms 
  Biochemical function     oxidoreductase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0610007104 Proc Natl Acad Sci U S A 104:473-478 (2007)
PubMed id: 17197414  
 
 
Molecular insights into substrate recognition and catalysis by tryptophan 2,3-dioxygenase.
F.Forouhar, J.L.Anderson, C.G.Mowat, S.M.Vorobiev, A.Hussain, M.Abashidze, C.Bruckmann, S.J.Thackray, J.Seetharaman, T.Tucker, R.Xiao, L.C.Ma, L.Zhao, T.B.Acton, G.T.Montelione, S.K.Chapman, L.Tong.
 
  ABSTRACT  
 
Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) constitute an important, yet relatively poorly understood, family of heme-containing enzymes. Here, we report extensive structural and biochemical studies of the Xanthomonas campestris TDO and a related protein SO4414 from Shewanella oneidensis, including the structure at 1.6-A resolution of the catalytically active, ferrous form of TDO in a binary complex with the substrate L-Trp. The carboxylate and ammonium moieties of tryptophan are recognized by electrostatic and hydrogen-bonding interactions with the enzyme and a propionate group of the heme, thus defining the L-stereospecificity. A second, possibly allosteric, L-Trp-binding site is present at the tetramer interface. The sixth coordination site of the heme-iron is vacant, providing a dioxygen-binding site that would also involve interactions with the ammonium moiety of L-Trp and the amide nitrogen of a glycine residue. The indole ring is positioned correctly for oxygenation at the C2 and C3 atoms. The active site is fully formed only in the binary complex, and biochemical experiments confirm this induced-fit behavior of the enzyme. The active site is completely devoid of water during catalysis, which is supported by our electrochemical studies showing significant stabilization of the enzyme upon substrate binding.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. The structure of TDO. (a) Schematic representation of the structure of the monomer of X. campestris TDO. The -helices are shown in yellow and labeled. Heme is shown in gray, and L-Trp is shown in orange (labeled W). The water molecule is shown as a red sphere (labeled wat). (b) Schematic representation of the tetramer of X. campestris TDO. The four monomers are colored in yellow, cyan, violet, and green. Helices in the tetramer interface are labeled. The Trp molecules in the tetramer interface are also shown. Produced with Molscript (35) and rendered with Raster3D (36).
Figure 3.
Fig. 3. Molecular basis for substrate recognition by TDO. (a) Final 2F[o]–F[c] electron density at 1.6-Å resolution for heme, L-Trp, and a water in the active site. Contoured at 1 . (b) Stereo drawing showing the active site of X. campestris TDO in the binary complex with L-Trp. The segment in cyan is from another monomer of the tetramer. Hydrogen-bonding interactions are indicated with dashed lines in magenta. (c) Overlay of the structures of the free enzyme (in orchid) and the binary complex (yellow and cyan) in the active-site region. Regions of conformational differences are indicated with the red arrows. (d) Overlay of the active-site region of the second monomer (in green) and that of the first monomer (in yellow). Only the side-chain atoms of Trp are shown in the second monomer (in magenta). (e) Final 2F[o]–F[c] electron density at 1.6-Å resolution for heme, L-Trp, and a water in the active site of the second TDO molecule in the crystal. Contoured at 1 . Two conformations for the main chain atoms are shown, but neither fit the density well. For the stereo version of c and d, please see SI Fig. 7. Produced with Molscript (35) and rendered with Raster3D (36).
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21351297 E.Olsson, A.Martinez, K.Teigen, and V.R.Jensen (2011).
Formation of the iron-oxo hydroxylating species in the catalytic cycle of aromatic amino acid hydroxylases.
  Chemistry, 17, 3746-3758.  
21170645 H.J.Yuasa, and H.J.Ball (2011).
Molecular evolution and characterization of fungal indoleamine 2,3-dioxygenases.
  J Mol Evol, 72, 160-168.  
19948665 J.E.Voss, S.W.Scally, N.L.Taylor, S.C.Atkinson, M.D.Griffin, C.A.Hutton, M.W.Parker, M.R.Alderton, J.A.Gerrard, R.C.Dobson, C.Dogovski, and M.A.Perugini (2010).
Substrate-mediated stabilization of a tetrameric drug target reveals Achilles heel in anthrax.
  J Biol Chem, 285, 5188-5195.
PDB code: 3hij
20361220 L.Capece, A.Lewis-Ballester, D.Batabyal, N.Di Russo, S.R.Yeh, D.A.Estrin, and M.A.Marti (2010).
The first step of the dioxygenation reaction carried out by tryptophan dioxygenase and indoleamine 2,3-dioxygenase as revealed by quantum mechanical/molecular mechanical studies.
  J Biol Inorg Chem, 15, 811-823.  
20715188 L.Capece, M.Arrar, A.E.Roitberg, S.R.Yeh, M.A.Marti, and D.A.Estrin (2010).
Substrate stereo-specificity in tryptophan dioxygenase and indoleamine 2,3-dioxygenase.
  Proteins, 78, 2961-2972.  
20353179 R.M.Davydov, N.Chauhan, S.J.Thackray, J.L.Anderson, N.D.Papadopoulou, C.G.Mowat, S.K.Chapman, E.L.Raven, and B.M.Hoffman (2010).
Probing the ternary complexes of indoleamine and tryptophan 2,3-dioxygenases by cryoreduction EPR and ENDOR spectroscopy.
  J Am Chem Soc, 132, 5494-5500.  
19805032 A.Lewis-Ballester, D.Batabyal, T.Egawa, C.Lu, Y.Lin, M.A.Marti, L.Capece, D.A.Estrin, and S.R.Yeh (2009).
Evidence for a ferryl intermediate in a heme-based dioxygenase.
  Proc Natl Acad Sci U S A, 106, 17371-17376.  
19218188 E.Fukumura, H.Sugimoto, Y.Misumi, T.Ogura, and Y.Shiro (2009).
Cooperative binding of L-trp to human tryptophan 2,3-dioxygenase: resonance Raman spectroscopic analysis.
  J Biochem, 145, 505-515.  
19767648 E.Nickel, K.Nienhaus, C.Lu, S.R.Yeh, and G.U.Nienhaus (2009).
Ligand and substrate migration in human indoleamine 2,3-dioxygenase.
  J Biol Chem, 284, 31548-31554.  
18493661 A.Sheoran, A.King, A.Velasco, J.M.Pero, and S.Garneau-Tsodikova (2008).
Characterization of TioF, a tryptophan 2,3-dioxygenase involved in 3-hydroxyquinaldic acid formation during thiocoraline biosynthesis.
  Mol Biosyst, 4, 622-628.  
19021508 S.J.Thackray, C.G.Mowat, and S.K.Chapman (2008).
Exploring the mechanism of tryptophan 2,3-dioxygenase.
  Biochem Soc Trans, 36, 1120-1123.  
17890323 F.Delaspre, C.G.Nieto Peñalver, O.Saurel, P.Kiefer, E.Gras, A.Milon, C.Boucher, S.Genin, and J.A.Vorholt (2007).
The Ralstonia solanacearum pathogenicity regulator HrpB induces 3-hydroxy-oxindole synthesis.
  Proc Natl Acad Sci U S A, 104, 15870-15875.  
17588214 F.Forouhar, A.Kuzin, J.Seetharaman, I.Lee, W.Zhou, M.Abashidze, Y.Chen, W.Yong, H.Janjua, Y.Fang, D.Wang, K.Cunningham, R.Xiao, T.B.Acton, E.Pichersky, D.F.Klessig, C.W.Porter, G.T.Montelione, and L.Tong (2007).
Functional insights from structural genomics.
  J Struct Funct Genomics, 8, 37-44.
PDB codes: 1rty 1sqs 1tm0 1zbp 2hd3 2nv4 2oys
18026683 H.J.Yuasa, M.Takubo, A.Takahashi, T.Hasegawa, H.Noma, and T.Suzuki (2007).
Evolution of vertebrate indoleamine 2,3-dioxygenases.
  J Mol Evol, 65, 705-714.  
18073103 W.A.Hendrickson (2007).
Impact of structures from the protein structure initiative.
  Structure, 15, 1528-1529.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.